Nat Med: genetic variation may help prevent Alzheimer's disease

February 14, 2020 / biourn / -- a new study by researchers at the Massachusetts General Hospital (MGH) and the Schepens Institute of Ophthalmology at the University of Antioquia offers insights into why some people may be more resistant to Alzheimer's than others These findings may lead to strategies to delay or prevent the disease Some people with mutations known to cause early-onset Alzheimer's disease don't show symptoms until they are very old - much later than expected Studies of these people may reveal genetic variations that reduce the risk of Alzheimer's and other forms of dementia In the study, published in nature medicine, Dr yakeel t Quiroz, a clinical neuropsychologist, neuroimaging researcher and her colleagues at MGH, described a patient from a Colombian family of more than 6000 members who had no cognitive impairment before the age of 70, more than 30 years later than the typical onset Photo source: Nature Medicine's relatives developed dementia symptoms in their 40s Like these patients, this patient carries a e280a mutation in the presenilin 1 (PSEN1) gene, which has been shown to cause early-onset Alzheimer's disease She also has two copies of the gene variation called Christchurch Christchurch is named after a New Zealand city It was first found in the apoE3 gene (apoe3ch) The team was unable to confirm that any other family member with two copies of the mutation also carried the PSEN1 e280a mutation In the analysis of 117 family members, 6% of them carried one apoe3ch gene mutation, including 4 people with PSEN1 e280a gene mutation Their average age was 45 years old, with signs of mild cognitive impairment Imaging examination showed only slight neurodegenerative changes in the brain Surprisingly, the patient had abnormally high levels of amyloid deposition in his brain, a sign of Alzheimer's disease; however, the number of tau tangles, another sign of the disease, was relatively limited The researchers suspect that carrying two copies of the apoe3ch variant may delay the clinical onset of Alzheimer's disease by limiting tau pathology and neurodegeneration "This single case has opened a new door for the treatment of Alzheimer's disease, which is more based on the resistance to Alzheimer's disease pathology than the cause of the disease In other words, instead of focusing on reducing pathology as has traditionally been done in this area, it's promoting resistance in the face of major brain pathology, "Quiroz said ApoE3 is a form of ApoE gene, which is the main susceptible gene of late-onset Alzheimer's disease The ApoE gene provides the instructions for making apoE, which is involved in the metabolism of fat in the body Experiments show that apoe3ch may reduce the ability of apoE to bind to a kind of glycoprotein called heparin sulfate proteoglycan (HSPG), which is related to β - amyloid protein and tau protein "This finding suggests that the combination of ApoE and HSPG has the potential to treat Alzheimer's disease, even at high levels of amyloidosis," said Dr Joseph f arboleda Velasquez, co-author of the study "This study highlights the importance of apoE in the development, treatment and prevention of Alzheimer's disease "Said Dr Eric M Reiman, co-author of the study "We hope that our findings will stimulate the discovery of drugs and gene therapy related to apoE, so that we can test them in treatment and prevention studies as soon as possible "Reference: yakeel t Quiroz et al Resistance to automatic domestic Alzheimer's disease in an apoE3 Christchurch homozygote: a case report, Nature Medicine (2019) Doi: 10.1038/s41591-019-0611-3